The present invention relates to prostaglandin analogs which are platelet aggregation inhibitors. In particular, heterocyclic oxazolidinone and thiazolidinone analogs are thus useful.
A number of classes of compounds have been shown to be platelet aggregation inhibitors in vitro. Prostaglandins and their analogs, different in structure from those of the invention herein, cyclooxygenase inhibitors, phosphodiesterase inhibitors, and membrane active compounds are examples of classes whose mechanism of action is understood. In addition, a class of miscellaneous compounds, whose mechanism of action is not known, including, for example, ticlopidine and adenosine, has also been used. Although the above compounds are active in vitro and in some animal model systems, there is, at the present time, no compound clinically verified to inhibit platelet aggregation in human beings, with the exception of aspirin for use in prevention of stroke (prior to any history thereof) in males.
Therefore, there remains a need for a satisfactory clinically usable platelet aggregation inhibitor. The compounds of the present invention are analogs of prostaglandins. Prostaglandins are a class of naturally occurring C.sub.20 fatty acids which are derived from three fatty acids essential to the human diet. A number of natural prostaglandins are known which are variations on the general structure ##STR4## in which the cyclopentane ring is oxidized, and a hydroxyl group appears in the C.sub.12 to C.sub.20 side chain.
Compounds known in the art which are closest in structure to those of the present invention are those prostaglandin analogs found in U.S. Pat. Nos. 4,059,587 and 4,102,888 which disclose heterocyclic forms of prostaglandins having different ring systems from those of the present invention.